(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA was host to the Poster Session A: Prostate Cancer. Dr. Moein Moradpour presented Abstract 259: Evaluating survival in aggressive variant prostate cancer patients undergoing PSMA radioligand therapy.
Dr. Moradpour opened his poster by emphasizing that aggressive variant prostate cancer (AVPC) is a distinct subtype of metastatic castration-resistant prostate cancer (mCRPC) defined by high-risk clinical and molecular features. AVPC is associated with poorer overall survival and limited responsiveness to androgen receptor-targeted therapy, though it may exhibit sensitivity to chemotherapy.
This retrospective study aimed to assess the outcomes of AVPC in patients treated with Prostate-Specific Membrane Antigen (PSMA) radioligand therapy (RLT). The investigators analyzed data from 206 mCRPC patients who received ¹⁷⁷Lu-PSMA RLT at two academic centers.
Patients were classified as having AVPC based on the presence of at least one of the following eight criteria:
AVPC patients were categorized into AVPC-C, based on clinicopathological criteria, and AVPC-MS, based on molecular signature criteria.
Among the 201 patients analyzed, 53 met the criteria for AVPC. Patients with AVPC had a median age of 65.4 years and a median PSA at diagnosis of 361.7 ng/mL. Notably, The PSA₅₀ response rate was 61% in the AVPC group compared to 60% in the non-AVPC group. Median overall survival (OS) was 223 days for AVPC patients and 305 days for non-AVPC patients; however, this difference did not reach statistical significance (log-rank p = 0.179).
Among AVPC patient subgroups, median OS was significantly shorter in AVPC-C compared to non-AVPC patients (305.6 vs. 196.4 days, p = 0.002), and in AVPC compared to non-AVPC patients (305.6 vs. 223.4 days, p = 0.01). However, no significant OS difference was observed between AVPC-MS and AVPC-C patients (p = 0.13).
Dr. Moradpour concluded
- Patients with AVPC may derive benefit from PSMA radioligand therapy and should be considered for treatment if eligible
- Despite similar PSA50 response rates, the presence of AVPC features (clinicopathological or molecular signature) remains a negative prognostic factor
- There was no survival difference between the subtypes of AVPC treated with RLT in this study
- Further studies are needed to better characterize this patient population and optimize therapeutic strategies.
Presented by: Moein Moradpour, MD, Radiology Department at the University of California, San Francisco (UCSF). San Francisco, CA, United States.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.